Background: Machine learning methods have been developed to predict the likelihood of a given event or classify patients into two or more diagnostic categories. Digital twin models, which forecast entire trajectories of patient health data, have potential applications in clinical trials and patient management. Methods: In this study, we apply a digital twin model based on a variational autoencoder to a population of patients who went on to experience an ischemic stroke. The digital twin’s ability to model patient clinical features was assessed with regard to its ability to forecast clinical measurement trajectories leading up to the onset of the acute medical event and beyond using International Classification of Diseases (ICD) codes for ischemic stroke and lab values as inputs. Results: The simulated patient trajectories were virtually indistinguishable from real patient data, with similar feature means, standard deviations, inter-feature correlations, and covariance structures on a withheld test set. A logistic regression adversary model was unable to distinguish between the real and simulated data area under the receiver operating characteristic (ROC) curve (AUC_adversary = 0.51). Conclusion: Through accurate projection of patient trajectories, this model may help inform clinical decision making or provide virtual control arms for efficient clinical trials.

Background: Racial disparities in health care are well documented in the United States. As machine learning methods become more common in health care settings, it is important to ensure that these methods do not contribute to racial disparities through biased predictions or differential accuracy across racial groups. Objective: The goal of the research was to assess a machine learning algorithm intentionally developed to minimize bias in in-hospital mortality predictions between white and nonwhite patient groups. Methods: Bias was minimized through preprocessing of algorithm training data. We performed a retrospective analysis of electronic health record data from patients admitted to the intensive care unit (ICU) at a large academic health center between 2001 and 2012, drawing data from the Medical Information Mart for Intensive Care–III database. Patients were included if they had at least 10 hours of available measurements after ICU admission, had at least one of every measurement used for model prediction, and had recorded race/ethnicity data. Bias was assessed through the equal opportunity difference. Model performance in terms of bias and accuracy was compared with the Modified Early Warning Score (MEWS), the Simplified Acute Physiology Score II (SAPS II), and the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE). Results: The machine learning algorithm was found to be more accurate than all comparators, with a higher sensitivity, specificity, and area under the receiver operating characteristic. The machine learning algorithm was found to be unbiased (equal opportunity difference 0.016, P=.20). APACHE was also found to be unbiased (equal opportunity difference 0.019, P=.11), while SAPS II and MEWS were found to have significant bias (equal opportunity difference 0.038, P=.006 and equal opportunity difference 0.074, P<.001, respectively). Conclusions: This study indicates there may be significant racial bias in commonly used severity scoring systems and that machine learning algorithms may reduce bias while improving on the accuracy of these methods.

Background: A high number of patients who are hospitalized with COVID-19 develop acute respiratory distress syndrome (ARDS). Objective: In response to the need for clinical decision support tools to help manage the next pandemic during the early stages (ie, when limited labeled data are present), we developed machine learning algorithms that use semisupervised learning (SSL) techniques to predict ARDS development in general and COVID-19 populations based on limited labeled data. Methods: SSL techniques were applied to 29,127 encounters with patients who were admitted to 7 US hospitals from May 1, 2019, to May 1, 2021. A recurrent neural network that used a time series of electronic health record data was applied to data that were collected when a patient’s peripheral oxygen saturation level fell below the normal range (<97%) to predict the subsequent development of ARDS during the remaining duration of patients’ hospital stay. Model performance was assessed with the area under the receiver operating characteristic curve and area under the precision recall curve of an external hold-out test set. Results: For the whole data set, the median time between the first peripheral oxygen saturation measurement of <97% and subsequent respiratory failure was 21 hours. The area under the receiver operating characteristic curve for predicting subsequent ARDS development was 0.73 when the model was trained on a labeled data set of 6930 patients, 0.78 when the model was trained on the labeled data set that had been augmented with the unlabeled data set of 16,173 patients by using SSL techniques, and 0.84 when the model was trained on the entire training set of 23,103 labeled patients. Conclusions: In the context of using time-series inpatient data and a careful model training design, unlabeled data can be used to improve the performance of machine learning models when labeled data for predicting ARDS development are scarce or expensive.

Background: Acute heart failure (AHF) is associated with significant morbidity and mortality. Effective patient risk stratification is essential to guiding hospitalization decisions and the clinical management of AHF. Clinical decision support systems can be used to improve predictions of mortality made in emergency care settings for the purpose of AHF risk stratification. In this study, several models for the prediction of seven-day mortality among AHF patients were developed by applying machine learning techniques to retrospective patient data from 236,275 total emergency department (ED) encounters, 1881 of which were considered positive for AHF and were used for model training and testing. The models used varying subsets of age, sex, vital signs, and laboratory values. Model performance was compared to the Emergency Heart Failure Mortality Risk Grade (EHMRG) model, a commonly used system for prediction of seven-day mortality in the ED with similar (or, in some cases, more extensive) inputs. Model performance was assessed in terms of area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. Results: When trained and tested on a large academic dataset, the best-performing model and EHMRG demonstrated test set AUROCs of 0.84 and 0.78, respectively, for prediction of seven-day mortality. Given only measurements of respiratory rate, temperature, mean arterial pressure, and FiO₂, one model produced a test set AUROC of 0.83. Neither a logistic regression comparator nor a simple decision tree outperformed EHMRG. Conclusions: A model using only the measurements of four clinical variables outperforms EHMRG in the prediction of seven-day mortality in AHF. With these inputs, the model could not be replaced by logistic regression or reduced to a simple decision tree without significant performance loss. In ED settings, this minimal-input risk stratification tool may assist clinicians in making critical decisions about patient disposition by providing early and accurate insights into individual patient’s risk profiles.

Objective: In the wake of COVID-19, the United States (U.S.) developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans deemed to be at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness, and may therefore be of limited use in decisions surrounding resource allocation to vulnerable populations. The objective of this study was to evaluate a machine learning algorithm for prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records.

Diagnosis and appropriate intervention for myocardial infarction (MI) are time‐sensitive but rely on clinical measures that can be progressive and initially inconclusive, underscoring the need for an accurate and early predictor of MI to support diagnostic and clinical management decisions. The objective of this study was to develop a machine learning algorithm (MLA) to predict MI diagnosis based on electronic health record data (EHR) readily available during Emergency Department assessment. An MLA was developed using retrospective patient data. The MLA used patient data as they became available in the first 3 h of care to predict MI diagnosis (defined by International Classification of Diseases, 10th revision code) at any time during the encounter. The MLA obtained an area under the receiver operating characteristic curve of 0.87, sensitivity of 87% and specificity of 70%, outperforming the comparator scoring systems TIMI and GRACE on all metrics. An MLA can synthesize complex EHR data to serve as a clinically relevant risk stratification tool for MI.